Influence of platelet-derived endothelial cell growth factor/thymidine phosphorylase on the cell cycle in head and neck squamous cell carcinoma in vitro

Oncol Rep. Jul-Aug 2003;10(4):967-71.

Abstract

Platelet-derived endothelial cell growth factor (PD-ECGF) was isolated as an endothelial mitogen from platelets and demonstrated to have angiogenic activity and thymidine phosphorylase (TP) activity. It was reported that the overexpression of PD-ECGF occurred with the rapid tumor growth in vivo. In this study, we transfected PD-ECGF into the head and neck squamous cell carcinoma cell line IMC-3 and investigated the property of transfectants in vitro. Highly overexpressed PD-ECGF transfectants rapidly grew compared with parental cells and control vector (CV) transfectants (p<0.05). The expression of cyclin D1 and cyclin E were more enhanced in PD-ECGF transfectants than parental cells and CV transfectants, while the p27kip1 was inhibited in PD-ECGF transfectants. In PD-ECGF transfectants, S and G2/M-phase cells rapidly increased compared with parental cells and CV transfectants. These results showed that the cancer cell line with high expression of PD-ECGF had a rapid cell cycle and consequently facilitated rapid cell growth not only in vivo but also in vitro. Furthermore, the inhibitor of thymidine phosphorylase (TPI) suppressed the cell cycle and rapid cell growth that were acquired by PD-ECGF transfection. Since PD-ECGF was reported to be an independent, poor prognosis factor for head and neck cancer, TPI might be useful for the inhibition of cancer cell growth.

MeSH terms

  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism
  • Cyclin D1 / metabolism
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / physiology*
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / pathology*
  • Humans
  • In Vitro Techniques
  • Thymidine Phosphorylase / genetics
  • Thymidine Phosphorylase / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Cyclin E
  • Enzyme Inhibitors
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Thymidine Phosphorylase
  • Cyclin-Dependent Kinases